A Novel View of Cancer Stem Cells

I follow developing work on cancer stem cells with some interest; there is at least some chance that a focus on cancer stem cells will lead to a grand simplification in treating many forms of cancer. Simplification here means a clearly identifiable type of cell to attack to stop a particular cancer in its tracks. A requirement to destroy specific clearly identifiable classes of cell plays to the strengths of biotechnologies now in development, and any area in which this is the case will see very effective therapies a decade from now. This would be a wonderful thing in the case of cancer, a most fearsome age-related condition, the malfunctioning of our most fundamental biochemical machinery. We should all be concerned about the cancer with our name on it; it's waiting out there for you to live long enough to meet it.

Nature recently published a novel perspective on cancer stem cells and the backstory behind how we ended up with the biochemistry we have. Well worth reading as a good example of how researchers attempt to fit theories around the evidence to date:

Our cells are constantly being replaced in vast numbers: the human body typically contains about a hundred trillion cells, and many billions are shed and replaced every day.

If this happened simply by replication of the various specialized cells in each tissue, our tissues would evolve: mutations would arise, and some would spread. In particular, mutant cells that don't do their specialized job so well tend to replicate more quickly than non-mutants, and so gain a competitive advantage, freeloading off the others. In such a case, our wonderfully wrought bodies could grind to a halt.

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To renew themselves, epithelial tissues retain a population of undifferentiated stem cells, like the unformed cells present in embryos, that have the ability to grow into different types of cells. When replacements are needed, some of these stem cells divide to make transient amplifying cells (TACs). The TACs then divide several times, and Pepper and his co-workers think that each division produces cells that are a little more developed into mature tissue cells.

All this costs a lot of metabolic energy, so it is not very efficient. But, the researchers say, it means that the functions of self-replication and proliferation are divided between separate groups of cells. The stem cells replicate, but only a little, and so there's not much chance for mutations to arise or for selective pressure to fix them in place. The proliferating TACS may mutate, but they aren't simply copying themselves, so there isn't any direct competition between the cells to create an evolutionary pressure. As a result, evolution can't get started.

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Whereas conventional wisdom has it that cancer is caused by some genetic mutation that leads cells to proliferate uncontrollably, this new picture implies that the problem would lie with TAC mutations that interfere with differentiation - so that a TAC cell ends up just copying itself instead of producing cells on the next rung up on the way to mature tissue cells.

Under this viewpoint, complex organisms - and our bodies - have evolved over generations to not evolve within a lifetime. Evolved to be cooperative machinery, rather than a collection of cells all trying to get ahead as individuals. Cancer is a breakdown of the mechanisms of cooperation, making cells act more like selfish bacteria in a petri disk and less like a well-tuned machine.

As for other theories on cancer stem cells, this work points out a clear and defined set of characteristics to look for if you want to destroy cancer cells before cancer even gets underway. Work in the lab will validate or disprove this line of thinking within the next few years at the present pace of progress. Very promising times we live in.

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